Proteins are attractive bioavailability enhancers for poorly absorbed nutraceuticals or drugs, owing to their natural abundance, amphiphilic nature, and desirable biocompatibility. This study systematically investigated the preparation, characterization, and application of protein-based nanoparticles as effective nutraceutical/drug carriers.

Soy protein, one of the most widely utilized proteins, was firstly employed for preparing nanoparticles. The particle formation involved partial unfolding of protein molecules, limited aggregation in the presence of the antisolvent, crosslinking via chemical bonds, and refolding of the constituent monomers. Satisfactory encapsulation efficiency (EE) and time-dependent release of curcumin, a chemopreventive compound, were observed. The nanoparticles were further subjected to conjugation with folic acid, a cancer cell-targeting ligand. A pronounced increase in the accumulation in tumor cells such as Caco-2 was achieved upon folic acid conjugation, which demonstrated the potential of this technique for the targeted delivery of anti-cancer drugs. To overcome the rapid digestion of soy protein nanoparticles in the gastrointestinal tract, carboxymethyl chitosan was employed as a second coating layer by a simple ionic gelation method. The formed particles exhibited satisfactory EE for vitamin D3 and controlled releasing profile in vitro.

Beta lactoglobulin (BLG) as another protein of interest is a major component of whey protein, serving as a natural carrier for lipophilic nutrients. Our study suggested that the interaction between BLG and curcumin could be promoted by tuning the antisolvent content. A loading capacity (LC) and EE of up to 11% and 98% respectively could be achieved under the optimal conditions. Moreover, nanoparticles prepared with cationic beta-lactoglobulin (CBLG) were able to transport most of the encapsulated drug intact through the gastrointestinal (GI) tract owing to its desirable particle integrity. Other advantages of CBLG-based systems included superior mucoadhesion, permeation across the small intestine epithelia, and cellular uptake. Finally, as CBLG molecules/nanoparticles absorbed the negatively charged serum proteins in the cell culturing medium, their surface properties, cytotoxicity, and cellular uptake were significantly altered. This series of studies not only demonstrated the efficiency and versatility of protein-based nanoparticles as bioavailability enhancers but also shed some light on the mechanisms for the encapsulation, transport, and delivery of nutraceuticals or drugs.